Free radicals and the peroxidative processes caused by them have been known for a long time to be one of the causes of the structural and functional degradations of human tissues during aging and of a number of pathologies related to them: tumours; diabetes; hypertension; muscular excessive strain; radiation and sunburn damages; intoxications; ischemia; atherosclerosis; hyperthermia; cerebral traumas; inflammations; cataract; multiple sclerosis; Down syndrome, Parkinson's disease, Alzheimer's disease; dermatitis; muscular dystrophy; obesity; hyperlipidemia; hypercholesterolemia; tabagism; alcoholism, etc. (B. Cestaro, (1994), in "Per una vita inossidabile", ETASLIBRI--RCS Medicine, pp. 7-59; G. D. Bompiani, A. Galluzzo, (1990), in "Radicali Liberi in Fisiologia and Minerva Medica", pp. 3-280; Supplement to "The American Journal of Clinical Nutrition" vol. 53 (n. 1), 1991. pp. 1895-391S; "Radicali Liberi in Medicina", Periodici UTET Scientifici n. 1. dicembre 1993. pp. 1-57; "Lipid Peroxidation: part II Pathological Implications", (1987), Chem and Physics of Lipids, vol. 45 (n. 2-4), pp. 103-353).
Therefore it is important, in order to prevent the aging processes and related pathologies, to keep the concentration of the natural antioxidant molecules, ("free radical scavengers") which are the physiological defenses against free radicals, high both in the different tissues of the organism and in the blood stream, with which a continuous functional interchange occurs; in other words, blood (and the erythrocytes contained therein) can act as a carrier: 1) to provide the necessary antioxydants (both exogenous and deriving from, for example, the oral administration, and taken from endogenous deposits) to a certain tissue (which is at that time subjected to a specific pathological stress condition); 2) to drain the products from the peroxidative processes accumulated in a specific district of the organism.
It is therefore evident that an appropriate chemical-clinical evaluation of the sensitivity of plasma and/or of the erythrocytes (i.e. of the different tissues of the organism) to peroxidation can be an effective prognostic means to evaluate the efficiency of human antioxidant defenses and the capability of the body of defending against the damage induced by said dysmetabolic processes, typical of aging and of the above cited pathologies.
Carnosine (.beta.-alanyl-L-histidine) and some derivatives thereof (homocarnosine, acetylcarnosine, acetylhomocarnosine, etc.) have been known for some time to be among the most important natural antioxidant agents (Boldyrev A., Severin S., (1990), Adv. Enz. Reg., 30. 175-194; Kohen R. et al., (1988), Proc. Natl. Acad. Sci. USA, 85. 3175-79; Yoshikawa T. et al., (1991), Biochim. Biophys. Acta, 1115. 15-22) and the administration of these compounds would allow to cause an effective therapeutical activity in a number of the above mentioned pathologies (Davey C. L., (1960), Arch. Biochem. Biophys., 89. 303-308; Severin S., (1964); Proc. 6th Intern. Biochem. Congress, 45-61; Nagai K. and Suda T., (1988), Meth. Find. Exp. Clin. Pharmacol., 10. 497-507; Boldyrev A., (1990), Int. J. Biochem., 22. 129-132; Kurelle E. et al., (1991), Byul. Exp. Biol. Med., 112. 52-53; Boldyrev A. et al.; (1993), Int. J. Biochem., 25 1101-1107; Boldyrev A. et al., (1993), Mol. Chem. Neuropathol., 19. 185-192), particularly where the peroxidative damage induced by free radicals is one of the main causes in inducing and/or worsening the pathology. The antiradicalic activity of exogenous carnosine (or of the homologues thereof) is however restricted by the instability shown by said peptide towards the enzyme carnosinase, which is capable of hydrolyzing it into aminoacids components. The carnosinase is present both in the bloodstream and in the various tissue districts.
It has now been surprisingly found that the combination of carnosine with the branched amino acids leucine, isoleucine and valine induces an effect synergistic with the carnosine antioxidant activity, prolonging it in time, at equal doses. Since a direct antiradicalic effect of said amino acids (even if they are known to promote a therapeutical activity in different tissues, particularly in the skeletal muscle, thanks to their capability of increasing the cell energetic metabolism (R. Bernardi, in "Aminoacidi ed Esercizio", (1992), EDI-ERMES editore, Milan, Italy)), it is believed (without however limiting the scope of the invention) that such a synergistic effect can be ascribed to an inhibitory action on carnosinase, which prolongs the half-life of the circulating dipeptide and increases the bioavailability due to both the reaching of the specific tissue targets and the antioxidant action.
As an alternative, non-limiting interpretation, the increased antiradicalic effectiveness could be related to: 1) the cell energetic metabolic increase by the branched amino acids, which would lead to a reduction in the formation of free radicals, particularly those of the oxygen; 2) the indirect antioxidant action mediated by the cell activation induced by said amino acids, via unknown mechanisms and mediators.